Gene conversion between functional trypsinogen genes PRSS1 and PRSS2 associated with chronic pancreatitis in a six-year-old girl

Niels Teich, Zsófia Nemoda, Henrik Köhler, Wolfram Heinritz, Joachim Mössner, Volker Keim, Miklós Sahin-Tóth

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30 Citations (Scopus)

Abstract

Gene conversion - the substitution of genetic material from another gene - is recognized as the underlying cause of a growing number of genetic diseases. While in most cases conversion takes place between a normal gene and its pseudogene, here we report an occurrence of disease-associated gene conversion between two functional genes. Chronic pancreatitis in childhood is frequently associated with mutations of the cationic trypsinogen gene (serine protease 1; PRSS1). We have analyzed PRSS1 in 1106 patients with chronic pancreatitis, and identified a novel conversion event affecting exon 2 and the subsequent intron. The recombination replaced at least 289 nucleotides with the paralogous sequence from the anionic trypsinogen gene (serine protease 2; PRSS2), and resulted in the PRSS1 mutations c.86A>T and c.161A>G, causing the amino acid substitutions N29I and N54S, respectively. Analysis of the recombinant N29I-N54S double mutant cationic trypsinogen revealed increased autocatalytic activation, which was solely due to the N29I mutation. In conclusion, we have demonstrated that gene conversion between two functional paralogous trypsinogen genes can occur and cause genetically determined chronic pancreatitis. Hum Mutat 25:343-347, 2005.

Original languageEnglish
Pages (from-to)343-347
Number of pages5
JournalHuman mutation
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 27 2005

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Keywords

  • Gene conversion
  • PRSS1
  • PRSS2
  • Pancreatitis, chronic
  • SPINK1
  • Serine protease 1
  • Serine protease 2
  • Trypsinogen, anionic
  • Trypsinogen, cationic

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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